JPS61500302A - biomaterial - Google Patents

biomaterial

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Publication number
JPS61500302A
JPS61500302A JP59503807A JP50380784A JPS61500302A JP S61500302 A JPS61500302 A JP S61500302A JP 59503807 A JP59503807 A JP 59503807A JP 50380784 A JP50380784 A JP 50380784A JP S61500302 A JPS61500302 A JP S61500302A
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pleura
tanning
patient
treated
shows
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ケサラナサン・ヴエテイヴエトピライ
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バイオ・ノバ・ネオ・テクニクス・プロプライエタリー・リミテッド
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3687Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/42Respiratory system, e.g. lungs, bronchi or lung cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/40Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60Materials for use in artificial skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/40Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Botany (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Pulmonology (AREA)
  • Biotechnology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Immunology (AREA)
  • Materials Engineering (AREA)
  • Physiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)
  • Saccharide Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。 (57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

【発明の詳細な説明】 生 体 材 料 技術分野 本発明は生物学的環境において用いる新規な種類の材料に関するものである。特 に、この材料は、例えば外科ドレッシング(surgical dressin g)として、またはヘルニア、心臓弁、心臓の穴または他の欠陥を回復するため に人体の治療に用いることができる。ある場合には、本発明によって得られた材 料は透析および他の濾過処理に用いることができる。[Detailed description of the invention] raw material Technical field The present invention relates to a new class of materials for use in biological environments. Special This material can be used, for example, in surgical dressings. g) as or for repairing hernias, heart valves, holes in the heart or other defects; It can be used for human treatment. In some cases, the material obtained according to the invention The material can be used in dialysis and other filtration processes.

発明の開示 本発明の材料はグルタルアルデヒド タンニング処理軸1utaraldehy de tanning)を受ける動物壁側胸膜のシートからなる。また、本発明 は上記材料を外科組織移植として、または患者に施すドレッシングとして使用す ることができる。Disclosure of invention The material of the present invention is glutaraldehyde. It consists of a sheet of animal parietal pleura that undergoes detanning. Moreover, the present invention may use the above materials as surgical tissue grafts or as dressings applied to patients. can be done.

また、本発明は動物壁側胸膜のシートにグルタルアルデヒド タンニング処理を 施すことからなる生体適合性材料を製造する方法に関する。Additionally, the present invention applies glutaraldehyde tanning treatment to sheets of animal parietal pleura. The present invention relates to a method of manufacturing a biocompatible material comprising applying the same.

材料はグルタルアルデヒド タンニング処理前または後に照射することができる 。例えば、0.2〜5.0メガラドの照射を与えることができる。The material can be irradiated with glutaraldehyde before or after tanning treatment . For example, irradiation of 0.2 to 5.0 megarads can be provided.

最大有用性として、生体材料(biomaterial)は次のようにする必要 がある: 1、たな貯蔵できるようにする。For maximum utility, biomaterials should: There is: 1. Make storage possible.

2、広範囲にわたる大きさまたは形状で利用できるようにする。2. Be available in a wide range of sizes or shapes.

3、殺菌するようにする。3. Sterilize.

4、非抗原性にする。4. Make it non-antigenic.

5、環境要求として生物分解性または非生物分解性状態で利用できるようにする 。5. Be available in biodegradable or non-biodegradable state as per environmental requirements .

6、環境要求として上皮または内皮生長を支持するようにする。6. Environmental requirements to support epithelial or endothelial growth.

本発明により壁側胸膜を処理することによって、上記要件に適合する生体材料を 製造することができる。By treating the parietal pleura according to the present invention, a biomaterial that meets the above requirements can be obtained. can be manufactured.

胸膜は胸腔(thoracic cavity)および肺の薄い膜状内膜(me mbranous lining)である。胸腔をおおう胸膜は壁側胸膜と称さ れ、肺をおおう胸膜を内蔵(visceral)と称される。The pleura is the thin membranous lining of the thoracic cavity and lungs. It is branous lining). The pleura that covers the thoracic cavity is called the parietal pleura. The pleura covering the lungs is called the visceral membrane.

本発明においては中皮細胞の単一層でおおったゆるい結合組織からなる壁側胸膜 を使用する。結合組織において見出される他の成分はマクロファージ、血管、リ ンパ管、神経線維および脂肪細胞である。In the present invention, the parietal pleura consists of loose connective tissue covered with a single layer of mesothelial cells. use. Other components found in connective tissue include macrophages, blood vessels, and lymphocytes. lymphatic vessels, nerve fibers, and fat cells.

ある環境において、人間の胸膜を利用することができるが、しかし一般に、壁側 胸膜は牛、羊および豚の如き動物の新鮮な屠殺死体から得られる。この方法にお いて、60cm X 60cm正方形のような大きさの胸膜のシートを得ること ができる。特定用途において、胸膜は胎児子うしから得ることができる。In some circumstances, human pleura can be utilized, but generally parietal Pleura is obtained from freshly slaughtered carcasses of animals such as cows, sheep and pigs. This method and obtain a sheet of pleura with a size like 60cm x 60cm square. Can be done. In certain applications, pleura can be obtained from fetal calves.

図面の簡単な説明 ゛ 次に、本発明において生成した材料の臨床使用の例を添付図面を用いて詳細に説 明する: 第1図は本発明によって作ったタンニングした(tanned)牛胸膜のシート の壁側がわを示している。Brief explanation of the drawing゛ Next, an example of clinical use of the material produced in the present invention will be explained in detail using the attached drawings. Clarify: FIG. 1 is a sheet of tanned bovine pleura made according to the present invention. It shows the side of the wall.

第2図は同じ材料の内蔵がわを示している。Figure 2 shows a built-in gill of the same material.

第3図はタンニングした牛胸膜の1部分を示す顕微鏡写真である。FIG. 3 is a photomicrograph showing a portion of tanned bovine pleura.

第4図は最初の犬の6ケ月移植後に回収した心膜斑を示している。Figure 4 shows a pericardial plaque recovered after 6 months of transplantation in the first dog.

第5図は他の犬の3ケ月内移植後に回収した心膜斑を示している。Figure 5 shows a pericardial plaque recovered from another dog after transplantation within 3 months.

第6および7図は他の犬の3ケ月内移植後に回収した左心房斑および肺外側流斑 (pulmonary outflow patch)を示している。Figures 6 and 7 show the left atrial plaque and lateral lung plaque recovered after transplantation within 3 months from another dog. (pulmonary outflow patch).

第8図は他の犬の3ケ月内移植後に回収した肺外側流斑を示している。Figure 8 shows a pulmonary lateral plaque recovered from another dog after transplantation within 3 months.

第9図は肺動脈および第7図の肺外側流斑の結合にわたる顕微鏡写真を示してい る。Figure 9 shows a photomicrograph spanning the pulmonary artery and the junction of the lateral pulmonary plaques of Figure 7. Ru.

第10図は左心房および心房斑の結合にわたる部分を示す顕微鏡写真を示してい る。Figure 10 shows a photomicrograph showing the left atrium and the area spanning the atrial plaque junction. Ru.

発明を実施する好適例 本発明により生体材料を製造する代表的な方法において屠殺場から新しく得た壁 側胸膜のシートをその滑らかな(内蔵)表面を覆うガーゼの単一層と広げる。Preferred example for carrying out the invention Walls freshly obtained from a slaughterhouse in an exemplary method of producing biomaterials according to the present invention Spread the sheet of lateral pleura with a single layer of gauze covering its smooth (visceral) surface.

胸膜を食塩水中に入れて研究室に送り、ここですべて過剰の組織を伸ばし、かつ きれいにして50〜150ミクロン厚さの均一な膜を得る。この事は、胸膜をき れいな条件下でコルクまたは他の適当な材料のボ、−ド上で伸ばし、この材料の 縁をピン留めし、余分の組織を外科器具で除去し、次いでエーテル、クロロホル ムまたは他の脂肪溶剤または分散剤で処理して達成させる。The pleura is placed in saline and sent to the laboratory where all excess tissue is stretched out and Clean to obtain a uniform film 50-150 microns thick. This may cause the pleural Stretch it on a board of cork or other suitable material under clean conditions, and The edges are pinned and excess tissue is removed with surgical instruments, followed by ether and chloroform. This is achieved by treatment with silica or other fatty solvents or dispersants.

1次いで、ボード上にピン留で支持している伸ばし、かつきれいにした胸膜を食 塩水中で洗浄し、タンニング溶液の浴中に浸す。一般に、タンニング溶液は0. 5〜5重量%の濃度を有するpH2〜8の範囲のグルタルアルデヒドを緩衝する ことができ、胸膜を必要とする最終構造および結合性(intagrity)に 影響されるが15分〜72時間の範囲で変えうる時間にわたって浸漬することが できる。この処理によって生成物の非抗原性を与え、かつ殺菌する。また付加強 さを付与する。1. Next, the stretched and cleaned pleura, supported by pins on the board, is eaten. Wash in salt water and soak in a bath of tanning solution. Generally, the tanning solution is 0. Buffers glutaraldehyde in the pH range 2-8 with a concentration of 5-5% by weight and the final structure and integrity that requires the pleura. Soak for a period of time that can vary from 15 minutes to 72 hours can. This treatment renders the product non-antigenic and sterile. Also additional strength Gives a sense of security.

浸透性、強さおよび生物分解性の如き材料の特性はタンニング処理(濃度、pH および持続時間)を制御することによって、および次の処理によって著しく変え ることができる。。弱い生物分解性材料はトリプシンの如き酵素で処理する前ま たは後において適当にタンニング処理することによって;または照射、スパイク による機械的な穿孔、レーザー ビームまたは電子ビ−ム エツチングによる穿 孔によって得ることができる。他方において、材料に十分なグルタルアルデヒド 処理を施す。この場合、最大強さおよび非生物分解性は、例えば脈管系における 斑(patches) 、ヘルニア欠損修復のために、または腓回復(tend on repair)のために必要とされる。Material properties such as permeability, strength and biodegradability are determined by the tanning process (concentration, pH and duration), and by the following treatments: can be done. . Weakly biodegradable materials should be treated with enzymes such as trypsin. or by subsequent appropriate tanning treatment; or by irradiation, spikes. Mechanical drilling by laser beam or electron beam etching Can be obtained by holes. On the other hand, there is enough glutaraldehyde in the material Apply processing. In this case, the maximum strength and non-biodegradability are e.g. patches, for hernia defect repair or tendon on repair).

材料は照射によるグルタルアルデヒド処理により、またある場合には二酸化エチ レン処理により殺菌することができる。The material is treated with glutaraldehyde by irradiation and in some cases with ethyl dioxide. It can be sterilized by sterilization.

タンニング処理したおよび殺菌した材料は50%アルコール溶液中に貯蔵するこ とができる。あるいは、また使用前に生理的食塩水で再構成することができる。Tanned and sterilized materials should be stored in 50% alcohol solution. I can do it. Alternatively, it can also be reconstituted with saline before use.

あるいは、また生理的プラズマと同様にするためにリン酸塩緩衝食塩水に貯蔵す ることができる。Alternatively, also stored in phosphate buffered saline to resemble physiological plasma. can be done.

次の実験的手順は、本発明において生成した生体材料の利用を評価するために行 った。The following experimental procedures were performed to evaluate the use of the biomaterials produced in the present invention. It was.

麻酔した3匹の羊に、皮膚を切取って10cm X 10cmの傷を付けた。こ れらの傷にアルコール中に貯蔵した2゜5%グルタルアルデヒド処理した牛胸膜 を縫合して傷をおおった。胸膜それ自体をその場に縫い付けた。次いで、動物を 3ケ月間にわたり調べ、この間に材料は満足な外科ドレッシングとして作用した 。この場合、収縮せず、傷あとが残らず、かつ感染も生じなかった。Three anesthetized sheep were given a 10 cm x 10 cm wound in the skin. child Bovine pleura treated with 2.5% glutaraldehyde stored in alcohol was applied to these wounds. The wound was covered with stitches. The pleura itself was sewn in place. Then the animal tested over a three-month period, during which time the material acted as a satisfactory surgical dressing. . In this case, there was no shrinkage, no scarring, and no infection.

また材料は融合または退化せず、胸膜をタンニングおよび/まはは照射処理しな いで生物分解性が高まる場合でも、極めて良好な結果が得られた。The material also does not fuse or degenerate and does not tan and/or irradiate the pleura. Very good results were obtained even when the biodegradability was increased.

けるタンニング処理した牛胸膜の評価 内移植処理を5匹の犬について行った。この場合、アルカ1JP117.4に緩 衝し、72時間にわたり2.5%グルタルアルデヒドにおいてタンニング処理し た中壁側胸膜をタンニングして作った埋設材料を用いた。この材料を第1〜3図 に示す。第1図は壁側がわを示しており:第2図はタンニング後の内蔵がわを示 しており、および第3図はコラーゲン線維の内部構造が重なり合った材料の内蔵 表面上をおおう中皮細胞を示す顕微鏡写真を示している。Evaluation of tanned bovine pleura Endograft procedures were performed on 5 dogs. In this case, the Alka 1JP117.4 tanned in 2.5% glutaraldehyde for 72 hours. We used a burial material made by tanning the medial parietal pleura. This material is shown in Figures 1 to 3. Shown below. Figure 1 shows the wall side; Figure 2 shows the built-in side after tanning. and Figure 3 shows the internal structure of the material where the internal structure of collagen fibers overlaps. Figure 3 shows a photomicrograph showing mesothelial cells lining the surface.

処理する雑種(m1xed breeds)のすべての犬の体重は14〜25k gであった。これらの犬は0.05mg/ kgのチオベントン ナトリウムお よび0.1 mg/ kgのアセチルプロマシンを皮下的に前投薬した。普通麻 酔をチオベントン ナトリウムまたはメンヘキシタール ナトリウムで誘導し、 亜酸化窒素、ハロタンおよび酸素の混合物で維持した。All mongrel (m1xed) dogs we handle weigh between 14 and 25 kg. It was g. These dogs received 0.05 mg/kg of thiobentone sodium and 0.1 mg/kg of acetyl promachine subcutaneously. Ordinary hemp inducing intoxication with thiobentone sodium or menhexital sodium, Maintained on a mixture of nitrous oxide, halothane and oxygen.

麻酔した犬を横向き状態に置き、準備し、殺菌した布で包み、第4左肋間隙を介 して左トランスコスタル(transcostal)開胸を行った。5匹の犬の すべてに、6膜欠損および左心房付属体切断を行った。欠損をタンニングした胸 膜の斑で修復した。胸膜を欠損に血液と心筋層とが接触する内蔵表面で670プ ロレン(proIe−ne)で縫い合せた。3匹の犬においては、肺搏流出路( pulmonary out41ow tract)を長さ方向に切開し、胸膜 のガラセラ) (gusset)を血液と接触する内蔵表面と縫い合せた。処理 の終りに、傷は層内に閉鎖し、胸部をドレーンした(drained) 。Place the anesthetized dog on its side, prepare it, wrap it in a sterile cloth, and insert it through the 4th left intercostal space. A left transcostal thoracotomy was performed. five dogs All had six membrane defects and left atrial appendage transection. Breasts with tanned defects It was repaired with a patch of membrane. 670 plates on the internal surface where blood and myocardium come into contact with the pleura defective. Sewn with Loren (proIe-ne). In three dogs, the pulmonary outflow tract ( The pulmonary out41ow tract) is incised lengthwise, and the pleura is The gusset was sewn to the visceral surface that comes into contact with blood. process At the end of the procedure, the wound was closed in layers and the chest was drained.

5匹の犬のすべてが処理の後まで生存していた。5匹のうち4匹の犬を3ケ月目 に電気的に殺し、残りの1匹の犬を6ケ月目に殺した。すべての胸膜斑を種々の 部位から回収し、ダマタルアルデヒド中に固定し、次いで組織学的に調べた。All five dogs survived after treatment. 4 out of 5 dogs are 3 months old The dog was electrocuted and the remaining dog was killed at 6 months old. All pleural plaques in various They were harvested from the site, fixed in damataraldehyde, and then examined histologically.

上述する処理の概略を次表に示す: 実験の結果は次の通りである: おるにつれて周囲の心房材料と縮むのを確かめた。縮まなかった1つの心房斑は 滑らかで、かつつやのある血液触媒表面を有していた。外部表面、は比較的に密 着していなかった。組織学的に、コラーゲン構築は保持されていた。血液接触表 面は「内皮状」細胞を示して肺搏流出路ガウセットはすべて同一にした。これら はいかなる拡張(d i fat 1on)または収縮も明らかに示さなかった 。また、血液中接触表面は滑らかで、つやを有していた。組織学的に、コラーゲ ン構築は流れ表面における「内皮状」細胞によって保護されていた。A summary of the above processing is shown in the table below: The results of the experiment are as follows: I confirmed that the surrounding atrial material was shrinking as it fell. The one atrial plaque that did not shrink was It had a smooth, shiny blood catalyst surface. The external surface is relatively dense. I wasn't wearing it. Histologically, collagen architecture was preserved. blood contact table The surfaces show "endothelial-like" cells, and the lung outflow tract Gaussettes were all identical. these did not clearly show any expansion (di fat 1on) or contraction . In addition, the surface in contact with blood was smooth and glossy. Histologically, collagen The structure was protected by "endothelial-like" cells at the flow surface.

心膜斑 心膜斑はすべて同一にした。6膜の静止に対するちゅうは良好であった。周囲の 肺組織に対して壁側表面に幾分付着を有していた。内蔵心膜表面は非常に滑らか で、かつ心筋層に付着しなかった。pericardial plaque All pericardial plaques were the same. The stability of the 6 membranes was good. surrounding It had some attachment to the parietal surface to the lung tissue. Visceral pericardial surface is very smooth and did not adhere to the myocardium.

上述する結果を第4〜10図に基づいて説明する。第4図は犬Nα1において6 ケ月移植後の心膜斑を示している。第5図は犬Nα3の左心室心外膜の反射を断 ち切る心膜斑を示している。第6図は大No、4において3ケ月移植後の左心房 斑を示しており、および第7図は同じ犬からの肺搏流出路を示している。第8図 は犬Nα5の3ケ月における肺搏流出路を示している。The above results will be explained based on FIGS. 4 to 10. Figure 4 shows 6 at dog Nα1. It shows pericardial plaques after implantation. Figure 5 shows the left ventricular epicardial reflex of canine Nα3. It shows a tearing pericardial plaque. Figure 6 shows the left atrium after 3 months of transplantation in large No. 4. Figure 7 shows the pulmonary outflow tract from the same dog. Figure 8 shows the pulmonary outflow tract of dog Nα5 at 3 months old.

第9図は犬Nα4からの肺動脈(Pa)および肺流出斑(Pl)の結合を示して いる。「内皮状」細胞は肺動脈から胸膜炎上に延長して見ることができる。第1 0図は左心房から移植の組織への滑らかな転移を示している犬Nα4の左肩(A t)と胸膜斑(PI)との結合における外観を示している。Figure 9 shows the connection of the pulmonary artery (Pa) and pulmonary outflow tract (Pl) from canine Nα4. There is. "Endothelial-like" cells can be seen extending from the pulmonary artery onto the pleurisy. 1st Figure 0 shows the left shoulder of canine Nα4 (A t) and the appearance at the junction with the pleural plaque (PI).

上記結果は、タンニングした牛胸膜が好ましい生物学的パッチング(patch ing)材料および好ましい血液接触材料であることを示している。The above results indicate that tanned bovine pleura is preferable for biological patching. ing) materials and preferred blood contacting materials.

普通麻酔状態のそれぞれ300gの体重を有する5匹の雄のフードラド ウィス ター ネズミ(hooded wista−nradc)の左外側壁上に、2  ”c+n直径の全厚さの皮膚欠損を形成した。タンニングした牛胸膜を傷の大き さにカットし、その上に殺菌した布でかぶせて傷に接触する内蔵表面とで露出屠 肉(exposed panniculus carnosus。Five male hooded rats weighing 300g each under normal anesthesia. On the left lateral wall of the hooded wista-nradc, 2 A full-thickness skin defect of c+n diameter was created.The tanned bovine pleura was Cut it into pieces and place a sterile cloth over it to remove the exposed carcass with the built-in surface in contact with the wound. Meat (exposed panniculus carnosus.

をおおった。傷をパラフィンガーゼで保護し、胸をギブス包帯で包囲した。処理 中、すべてのネズミは生存させ、15日間にわたって観察した。ギブス包帯を4 〜15日目に取去った。この実験において、牛胸膜は72時間にわたり2.5% グルタルアルデヒド(重量/容積)中でタンニングし、アルカリpHに緩衝した 。covered. The wound was protected with paraffin gauze and the chest was wrapped with a cast bandage. process During the experiment, all rats were allowed to survive and observed for 15 days. Cast bandage 4 It was removed on day 15. In this experiment, bovine pleura was tested at 2.5% over 72 hours. Tanned in glutaraldehyde (wt/vol) and buffered to alkaline pH .

ギブス包帯を除去した時に、タンニングした牛胸膜外科ドレッシングの測定を行 った。Measurements were taken on the tanned bovine pleural surgical dressing when the cast was removed. It was.

これらの試験結果を次の表に示す2 4〜11日の間に5匹のうち3匹のネズミは寸法が減少し、1匹は僅かに縮んだ 。1匹のネズミは「ドレッシング」を失い、評価できなかった。The results of these tests are shown in the table below2. Between 4 and 11 days, 3 out of 5 rats decreased in size and 1 shrunk slightly. . One rat lost its "dressing" and could not be evaluated.

包帯を除去して24時間のうちに、ドレッシングを脱水し、ネズミをきれいにし た。また、上記試験結果は、タンニングした牛胸膜が生体外科ドレッシング(b io−surgical dressi口g)として満足に使用できることを示 上述する結果は、本発明により得られた材料が血液接触表面を与える埋設物また は移植片としての使用を包含する人体の欠損を修復する外科治療に広く適用する ことができる。Within 24 hours of removing the bandage, dehydrate the dressing and clean the mouse. Ta. In addition, the above test results show that the tanned bovine pleura was It has been shown that it can be satisfactorily used as an io-surgical dressi mouth g). The above-mentioned results demonstrate that the material obtained according to the invention can be used in implants or implants that provide a blood-contacting surface. has wide application in surgical treatment to repair defects in the human body, including use as a graft be able to.

国際調査報告 ^NIIEX To THE INTEAIIATIONAL 5EARCHR EPORT 0N111TERIIA丁1ONAL APPLICATION  No、PCT/AU 84/C10206Gll 2063675 DE 30 08542 FR2469927JP56075152EP 52288 DE  3042860 JP 57168920END OF ANNEXinternational search report ^NIIEX To THE INTEAI IATIONAL 5EARCHR EPORT 0N111TERIIA 1ONAL APPLICATION No, PCT/AU 84/C10206Gll 2063675 DE 30 08542 FR2469927JP56075152EP 52288 DE 3042860 JP 57168920END OF ANNEX

Claims (9)

【特許請求の範囲】[Claims] 1.グルタルアルデヒドタンニング処理を施した動物壁側胸膜のシートからなる ことを特徴とする生体材料。1. Consists of a sheet of animal parietal pleura treated with glutaraldehyde tanning A biomaterial characterized by: 2.胸膜を牛胸膜とした請求の範囲第1項記載の生体材料。2. The biomaterial according to claim 1, wherein the pleura is bovine pleura. 3.動物壁側胸膜のシートにグルタルアルデヒドタンニング処理を施すことを特 徴とする外科グラフトまたはドレッシングとして使用するのに適当な生体材料の 製造方法。3. Specifically, a sheet of animal parietal pleura is treated with glutaraldehyde tanning. of biomaterials suitable for use as surgical grafts or dressings Production method. 4.胸膜を牛胸膜とする請求の範囲第3項記載の方法。4. 4. The method according to claim 3, wherein the pleura is bovine pleura. 5.胸膜を伸ばし、余分の組織をきれいに整えてタンニング処理前に実質的に均 一な厚さの膜を形成する請求の範囲第3または4項記載の方法。5. Stretch the pleura and clean up any excess tissue to create a virtually even surface before the tanning process. 5. The method according to claim 3 or 4, wherein a film having a uniform thickness is formed. 6.胸膜を0.5〜5重量%の濃度を有するpH2〜8の範囲の緩衝グルタルア ルデヒド中でタンニング処理し、15分〜72時間の範囲内の時間にわたって浸 漬する請求の範囲第3,4または5項記載の方法。6. The pleura was treated with buffered glutamate in the pH range 2-8 with a concentration of 0.5-5% by weight. Tanning treatment in aldehyde and soaking for a time ranging from 15 minutes to 72 hours. 6. The method according to claim 3, 4 or 5, wherein the method comprises: 7.患者に適用する外科グラフトとしてまたはドレッシングとして請求の範囲第 1または2項において請求する材料を使用することを特徴とする患者の治療方法 。7. Claims No. 1 as a surgical graft or as a dressing applied to a patient. A method of treating a patient characterized by using the material claimed in item 1 or 2. . 8.患者に適用する外科グラフトとしてまたはドレッシングとして請求の範囲第 3〜7項のいづれか一つの項において請求する方法により製造した材料を使用す ることを特徴とする患者の治療方法。8. Claims No. 1 as a surgical graft or as a dressing applied to a patient. Using materials manufactured by the method claimed in any one of paragraphs 3 to 7. A method of treating a patient characterized by: 9.胸膜の内蔵表面に血液接触表面を与える請求の範囲第7または8項記載の方 法。9. The person according to claim 7 or 8, which provides a blood contact surface on the internal surface of the pleura. Law.
JP59503807A 1983-10-20 1984-10-17 biomaterial Pending JPS61500302A (en)

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